This invention relates to the field of determining cell properties from multispectral imaging of the cells' response to incident light.
Cervical cancer usually develops along a junction where two types of cervical cells meet. This junction changes during a woman's lifetime, as one cell type is transformed into another. The cells' DNA is accessed for this cellular transformation, increasing the chance for mutations that can lead to cancer. The cancer begins as a pre-cancerous lesion; if left untreated the lesion can deepen over time to become an invasive cancer. Other cell abnormalities have similar pre-cancerous development phases.
The conventional way to screen for cervical cancer is the Pap smear. In a Pap smear, a sample of cells is taken from the cervix and analyzed under a microscope by an expert (a cytotechnologist). Pap smear results are typically available after about one week. Pap smear analysis can generate from 10% to 50% false negative results and false positive results. A positive Pap smear result usually triggers a second Pap smear. A second positive Pap smear prompts a colposcopic examination, in which the cervix is examined with a low power microscope by a professional colposcopist. The colposcopic examination, like many methods for detecting cancerous and pre-cancerous cells, required that part of the tissue be biopsied. Less invasive methods and apparatus that can detect cell abnormalities could improve the quality of care and simultaneously reduce the cost.
Abnormal cells can display different light emission characteristics than normal cells. Many researchers have attempted to detect abnormal cells based on this difference. Garfield and Glassman, U.S. Pat. No. 5,450,857, tried to detect changes in cervical connective tissue associated with changes in cervical dilation or effacement. Their method illuminated the cervix with laser light of a selected wavelength, then measured fluorescent emissions. Their method could not provide information about response to multiple excitation wavelengths or differentiate among responses at different wavelengths or from different parts of the cervix. Accordingly, their method could not provide enough information to detect cell abnormalities.
Adelman, U.S. Pat. No. 3,945,371, described an apparatus for visual inspection of the interior of cavities with access only through restricted orifices. Adelman's invention comprised a fiberoptic probe and a low power light source. The image of the interior was projected to a translucent display screen. Adelman's invention only provided for visual inspection; it could not and did not excite the cavity interior with selected wavelengths of light or measure the response thereto.
Ramanujam et al., U.S. Pat. No. 5,421,339, described a method for detecting abnormalities in cervical cells based on induced fluorescence intensity. Light from a Nitrogen pumped dye laser illuminated a 1 mm spot on a cervix. A full spectrum of fluorescence response from the cells in the 1 mm spot was collected. The Nitrogen pumped dye laser was pulsed to differentiate it from background light. Nitrogen pumped dye lasers can be very difficult to use and have high maintenance requirements and low reliability, making them poorly suited for clinical application. Detectors suitable for collecting a full spectrum of fluoresced light from a pulsed laser are complicated and consequently expensive. The limitation to a single 1 mm spot makes screening of large areas of the cervix impossible. Ramanujam's instrument accordingly was suited for use following Pap smear screening, but was not suitable for use instead of Pap smear screening.
Dombrowski, U.S. Pat. No. 5,424,543, described an imaging spectroradiometer. The apparatus provided a sequence of spectral images, where each spectral image depicted the scene at a selected wavelength. The apparatus, however, did not allow for excitation of a target at selected wavelengths, and did not provide for a probe that could be used for imaging hard to access targets such as the cervix. Accordingly, Dombrowski's apparatus could only provide multispectral visualization of a scene and could not be used to determine cell properties.
Other instruments have been proposed that collect fluorescence data from multiple discrete spots of the target. These systems provide some spatial information through the detection at multiple spots. They do not, however, provide full image detection and thus provide no more information than would multiple uses of an instrument like that described by Ramanujam.
Other cell properties can also be of interest. For example, NADH can provide information about cell metabolism. Present methods of measuring NADH, however, are limited to single cell, tissue removal methods. As another example, hemoglobin oxygenation can provide useful diagnostic information. Present blood gas measurement systems, however, require blood samples to be sent to a laboratory for analysis.
Accordingly, there is an unmet need for a non-invasive method and apparatus adapted for use in determining properties characteristic of cells.